Differential Response of Large and Small Coronary Arteries to Nitroglycerin and Angiotensin: Autoregulation and Tachyphylaxis

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Large proximal and smaller distal coronary arteries respond differently to pharmacologic agents, but the role of autoregulation is not known. We examined this role in dogs by cannulating the main left coronary artery and a distal left anterior descending artery branch. With coronary flow held constant, the distal coronary artery pressure and the gradient from proximal to distal artery were proportional to the small and the large vessel resistance, respectively. At normal perfusion pressure, nitroglycerin injected directly into the coronary artery caused a transient fall in small vessel resistance and a prolonged decrease in large vessel resistance. During ischemia, when small vessels autoregulated and small vessel resistance was minimal, nitroglycerin lowered only large vessel resistance. Angiotensin injected directly into the coronary artery increased small and large vessel resistance; the slower response of large vessel resistance followed a passive dilation caused by increased perfusion pressure. Continuous infusions of nitroglycerin and angiotensin maintained dilation and constriction of large vessels, respectively, but small vessels demonstrated tachyphylaxis. Only adenosine infusion maintained dilation in both large and small vessels. In response to varying perfusion, small vessels autoregulated and large vessels responded passively to changes in perfusion pressure. We concluded that small coronary arteries respond to cardiac metabolism and demonstrate escape from prolonged dilation and constriction. Conversely, large vessels respond continuously to sustained mechanical and pharmacologic stimuli independently of the nutritional state of the myocardium.

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